Case Presentation: A 72-Year-Old Woman With Metastatic Colorectal Cancer

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EP: 1.Case Presentation: A 72-Year-Old Woman With Metastatic Colorectal Cancer

EP: 2.Maintenance Therapies in Metastatic Colorectal Cancer

EP: 3.Metastatic Colorectal Cancer: Regorafenib

EP: 4.Treatment Sequencing in Metastatic Colorectal Cancer

Kanwal Raghav, MBBS, MD: Today we’ll be discussing a case of a 72-year-old woman with metastatic colorectal cancer. This patient presented with a 2-month history of bloating and abdominal discomfort. Her last colonoscopy was about 2 years ago and was negative, and she also had some unintentional weight loss. With regard to her past medical history, it’s significant only because of a hysterectomy done about 12 years ago and high blood pressure, which is controlled with lisinopril.

During the clinic work-up, the patient was found to be anemic with an elevated CEA [carcinoembryonic antigen] of 6 ng/mL. The colonoscopy revealed a 9-cm mass in the ascending colon; biopsy of this showed a poorly differentiated adenocarcinoma. The molecular profiling showed a microsatellite stable tumor, which was KRAS, NRAS, and BRAF wild type. CT scan showed widespread lesions spread across the liver. The patient was diagnosed with stage IV colorectal cancer, and the ECOG PS [performance status] of the patient was 1.

At that time, the patient was started on treatment with bevacizumab and FOLFOX [5-fluorouracil, leucovorin, oxaliplatin]. The patient received about 4 months of this treatment with scans at 2- and 4-months showing response. This was followed by maintenance chemotherapy between May 2018 and June 2019. In June 2019, the patient had increasing symptoms of shortness of breath and fatigue, and scans showed disease progression in both the lungs and the liver. Patient was then switched to FOLFIRI [5-fluorouracil, leucovorin, irinotecan] and cetuximab and received this treatment until August 2020 with stable disease as the best response. In August 2020, the patient had progressive disease and was given regorafenib.

Interestingly, it’s strange that the patient developed this disease in a rather short interval from the last colonoscopy, which was completely negative. We also want to notice that certain comorbidities can affect our treatment decisions in metastatic colorectal cancer, like high blood pressure, especially whether it’s controlled. In this case it was controlled. With regard to molecular profiling, this patient has had some focused testing around RAS and BRAF, but I would have done either a next-generation-sequencing panel or at least have status for HER2 amplification on expression, and also NTRK fusions, which are also targeted with subsets. It’s very clear that the patient has an unresectable disease, and therefore surgery is definitely not an option. That’s what we’re dealing with. Furthermore, the PS of the patient is 1, which has implications in how aggressive you can be with cytotoxic chemotherapy. Those are a couple of points that are noteworthy. It should also be remembered that the patient has a right-sided colon cancer because they have a 9-cm ascending mass lesion.

The first-line therapy options are usually a combination of cytotoxic chemotherapy with a biologic attached to them. In some cases, the first-line cytotoxic option is a triplet cytotoxic which is 5-FU [5-fluorouracil], oxaliplatin, and irinotecan or FOLFOXIRI [5-fluorouracil, leucovorin, oxaliplatin, irinotecan] with bevacizumab. This patient would not qualify for that. The TRIBE2 study that established the survival benefit of FOLFOXIRI [5-fluorouracil, leucovorin, oxaliplatin, irinotecan], which is triplet cytotoxic over doublets, allowed only patients with ECOG PS 0, especially if they were beyond ages of 70—so 71 to 75 patients, and all of them had to have ECOG PS0. Anything less than that, we could have a lower ECOG PS.

As far as this patient is concerned, a doublet cytotoxic is very reasonable. This was combined with a biologic that is anti-VEGF attached to bevacizumab, which is a common biologic. In some patients who are RAS, BRAF wild-type, HER2-negative, and left-sided colon cancer, there is also a possibility of using an anti-EGFR agent, such as cetuximab or panitumumab, up front because those are the patients that benefit most from this. Because this patient has a right-sided tumor, the choice of bevacizumab with FOLFOX [5-fluorouracil, leucovorin, oxaliplatin] was a reasonable choice.

Transcript edited for clarity.

Case Overview: A 72-Year-Old Woman With Metastatic Colorectal Cancer

May 2018

Initial presentation

A 72-year-old woman reported a 2-month history of bloating and abdominal cramping, and an 8-pound unintentional weight loss

Her last screening colonoscopy when she was 70 years of age was negative

PMH: hysterectomy at age 60, high blood pressure well controlled with lisinopril

Clinical workup

Labs: Hg 8.4 g/dL, CEA 6 ng/mL

Colonoscopy revealed a 9-cm mass in ascending colon

Pathology: invasive, poorly differentiated adenocarcinoma

Molecular testing: KRAS, NRAS, and BRAF wildtype; microsatellite stable

CT scan revealed widespread lesions in the liver

Diagnosis: Stage 4 colorectal cancer

ECOG PS is 1

Treatment

The patient received systemic therapy with FOLFOX + bevacizumab for 6 cycles, which was well tolerated

Follow-up imaging at 2 months and 4 months showed response in liver lesions

The patient continued on bevacizumab maintenance

June 2019

• The patient presents with shortness of breath and fatigue
• CT CAP shows two new lung lesions and growth of liver lesions
• The patient is switched to FOLFIRI and cetuximab
• Follow-up imaging showed stable disease in liver and lungs

August 2020

• The patient reports severe fatigue
• CT CAP shows progression in the lungs and new bony lesions
• The patient is given regorafenib alone